The study will determine whether the anti-CD3 monoclonal antibody, teplizumab, can help to prevent or delay the onset of type 1 diabetes (T1D) in relatives determined to be at very high risk for developing the disease. Teplizumab has been studied in new onset type 1 diabetes for testing of efficacy and safety in previous studies; other studies are currently in progress. The results of previous studies indicate that teplizumab reduces the loss of insulin production during the first year after diagnosis in individuals with type 1 diabetes. The purpose of this study is to determine if teplizumab can interdict the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the "pre-diabetic" state and thereby prevent or delay the onset of type 1 diabetes.

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

Criteria are met for diabetes onset as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation. [ Time Frame: Elapsed time from random treatment to development of type 1 diabetes (or time of last contact among those enrolled and determined to be eligible) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

effects on teplizumab based on age, gender, race/ethnicity,weight, BMI, immunologic, genetic , demographic, and lifestyle factors. [ Time Frame: Longitudinal analysis will take place over time until diagnosis of diabetes; some secondary outcome measures will be monitored longer such as metabolic and immunological markers. ] [ Designated as safety issue: No ]

Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.

Drug: Teplizumab

intravenous infusions

Placebo Comparator: Placebo infusion

Intravenous infusion of placebo (saline) will be given for 14 consecutive days. Infusions will take approximately 30 minutes and will be followed by a two hour observation period.

Drug: Teplizumab

intravenous infusions

Detailed Description:

The study plans to enroll approximately 140-170 subjects between the ages of 8-45 years, over 2-3 years. The study is projected to last between 4-6 years, depending upon rate of enrollment and number of subjects who develop diabetes.

The main study objective is to determine whether intervention with teplizumab will prevent or delay the development of type 1 diabetes in high risk autoantibody positive non-diabetic relatives of individuals with T1D. Secondary outcomes are to include analyses of C-peptide and other measures from Oral Glucose Tolerance Testing (OGTT), safety, tolerability, and other mechanistic outcomes will be assessed during the study.

Eligibility

Ages Eligible for Study:

8 Years to 45 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Between ages of 8-45 years

Have a relative with type 1 diabetes

If first degree relative must be 8-45 years old (brother, sister, parent, offspring)

If second degree relative must be between 8-20 years old (niece, nephew, aunt, uncle, grandchild, cousin)

Abnormal glucose tolerance by OGTT confirmed with 7 weeks of baseline visit [fasting blood glucose greater than 110mg/dL or and less than 126 mg/dL OR 2 hour glucose greater or equal to 140 mg/dL and less than 200 mg/dL OR 30, 60, or 90 minute value on OGTT greater than or equal to 200 mg/dL]

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01030861